全文获取类型
收费全文 | 17842篇 |
免费 | 1412篇 |
国内免费 | 1593篇 |
专业分类
20847篇 |
出版年
2024年 | 42篇 |
2023年 | 226篇 |
2022年 | 607篇 |
2021年 | 1002篇 |
2020年 | 658篇 |
2019年 | 793篇 |
2018年 | 759篇 |
2017年 | 522篇 |
2016年 | 745篇 |
2015年 | 1114篇 |
2014年 | 1330篇 |
2013年 | 1384篇 |
2012年 | 1662篇 |
2011年 | 1471篇 |
2010年 | 898篇 |
2009年 | 817篇 |
2008年 | 902篇 |
2007年 | 799篇 |
2006年 | 722篇 |
2005年 | 671篇 |
2004年 | 518篇 |
2003年 | 473篇 |
2002年 | 369篇 |
2001年 | 297篇 |
2000年 | 277篇 |
1999年 | 271篇 |
1998年 | 170篇 |
1997年 | 158篇 |
1996年 | 181篇 |
1995年 | 136篇 |
1994年 | 154篇 |
1993年 | 98篇 |
1992年 | 113篇 |
1991年 | 108篇 |
1990年 | 79篇 |
1989年 | 72篇 |
1988年 | 48篇 |
1987年 | 55篇 |
1986年 | 38篇 |
1985年 | 28篇 |
1984年 | 37篇 |
1983年 | 18篇 |
1982年 | 14篇 |
1981年 | 9篇 |
1979年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
71.
小麦条锈病是影响杂交小麦普及推广的重要因素。文章利用基因推导法和SSR分子标记技术,研究了温光型两系杂交小麦恢复系MR168的抗条锈性遗传规律及其控制基因染色体位置。结果表明,MR168对CY29、CY31、CY32、CY33等条锈菌生理小种表现高抗至免疫;对SY95-71/MR168杂交组合的正反交F1、BC1、F2和F3群体分单株接种鉴定显示,MR168对CY32号小种的抗性受1对显性核基因控制,该抗病基因来源于春小麦品种辽春10号。利用集群分离分析法(Bulked segregant analysis,BSA)和简单重复序列(Simple sequence repeat,SSR)分子标记分析抗病亲本MR168、感病亲本SY95-71及183个F2代单株,发现了与MR168抗条锈病基因连锁的5个微卫星标记Xgwm273、Xgwm18、Xbarc187、Xwmc269、Xwmc406,并将该基因初步定位在1BS着丝粒附近,暂命名为YrMR168;构建了包含YrMR168的SSR标记遗传图谱,距离YrMR168最近的两个微卫星位点是Xgwm18和Xbarc187,遗传距离分别为1.9 cM和2.4 cM,这两个微卫星标记可用于杂交小麦抗条锈病分子标记辅助育种。 相似文献
72.
73.
用VeroE6细胞从12例水痘及带状疱疹病人水疱液中分离到10株病毒,分离阳性率为83.3%。10株病毒均具有使感染细胞圆缩、融合、脱落等典型的VZV局灶性细胞病变(CPE)特点,CPE随着传代次数增加而加快。用带状疱疹恢复期病人血清作间接免疫荧光染色镜检,可见典型的感染细胞核内荧光块。10株病毒感染细胞制成的抗原片,检测5例带状疱疹病人急性期及恢复期血清,荧光抗体滴度均有4倍以上增高。VZV对Vero细胞敏感;对沙鼠肾,胎兔肾,胎豚鼠肾、肺、脾原代单层细胞不敏感;对乳小白鼠不敏感。毒种在-20℃保存一周内死亡;但在30%脱脂牛奶、20%小牛血清及10%山梨醇Eagle’s液中,液体或真空冷冻干燥-100℃可保存二年以上。 相似文献
74.
Leptin对猪原代脂肪细胞脂解及其关键脂酶mRNA表达的影响 总被引:3,自引:0,他引:3
Leptin是由脂肪组织分泌的内源因子,在调节机体能量平衡过程中起重要作用.Leptin促进脂解的研究由来已久,但其作用机理尚不完善.本研究旨在通过系统检测关键脂酶mRNA的表达变化来探讨Leptin促进脂解的分子机理.运用形态学观察,油红O染色和RT-PCR鉴定培养的猪原代脂肪细胞;甘油测定试剂盒和游离脂肪酸(FFA)测定试剂盒分别检测甘油和FFA的释放;半定量RT-PCR检测关键脂酶mRNA的表达.结果显示:100 nmol/L的Leptin可显著上调ATGL、TGH-2、HSL、MGL和LPL mRNA的表达(P<0.01),但同时下调Perilipin mRNA的表达(P<0.01);Leptin呈浓度依赖性促进甘油的释放(P<0.01),但对FFA的释放影响不显著(P>0.05).以上结果提示,Leptin可能主要通过上调ATGL、MGL、LPL和下调Perilipin的表达促进猪原代脂肪细胞的脂解;同时推测,FFA释放的相对稳定可能是由Leptin通过上调UCPs的表达而增加FFA的消耗引起的. 相似文献
75.
Hailun Zheng Xiquan Ke Dapeng Li Qiangwu Wang Jianchao Wang Xiaoyang Liu 《Cell cycle (Georgetown, Tex.)》2018,17(6):728-738
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. In China, the situation is even worse as cancer incidence and mortality continue to increase rapidly. Although tremendous progress has been made toward HCC treatments, the benefits for liver cancer patients are still limited. Therefore, it is necessary to identify and develop novel therapeutic methods. Neuronally expressed developmentally downregulated 4 (NEDD4), an E3 ubiquitin ligase, plays a critical role in the development and progression of various types of human cancers. In our study, NEDD4 acts as an oncoprotein in both QGY7703 and SMMC7721 liver cancer cell lines. We found that depletion of NEDD4 by siRNA transfection led to inhibition of cell growth, invasion and migration, and promotion of apoptosis. In contrast, overexpression of NEDD4 via plasmid transfection resulted in facilitated cell proliferation, invasion and migration, and decreased apoptosis. Importantly, we observed that tumor suppressor LATS1, also a core component of Hippo pathway, was negatively regulated by NEDD4 in liver cancer cells. Our findings suggested that NEDD4 may be involved in the HCC progression via regulating LATS1 associated signaling pathway. Therefore, targeting NEDD4-LATS1 signaling could be a potential therapeutic option for HCC treatment. 相似文献
76.
Xu Jiliang Zhang Xiaohui Zhang Zhengwang Zheng Guangmei Ruan Xiangfeng Zhang Keyin Xi Bo 《Frontiers of Biology in China》2006,1(2):174-181
Home range and habitat use of male Reeves’s pheasant (Syrmaticus reevesii) were studied during winter of 2001∼2002 and 2002∼2003 in the Dongzhai National Nature Reserve, Henan Province. Results from
five individuals of Reeves’s pheasant with over 30 relocations, indicated that the average size of home range was 10.03 ±
1.17 hm2 by Minimum Convex Polygon method, 8.60 ± 0.35 hm2 by 90% Harmonic Mean Transformation method, and 9.50 ± 1.90 hm2 by 95% Fixed Kernel method. It was observed that the winter range is smaller than that in the breeding season. The mean core
area of the home range was found to be 1.88 ± 0.37 hm2. Although the habitat composition of the core area varied greatly for individuals, a large part of the habitats used were
composed of confier and broadleaf mixed forests, masson pine forests, fir forests, and shrubs. Habitat use within the study
area was non-random, while habitats within home ranges were randomly used. Habitat use was dictated by tree diameter at breast
height, shrub height and coverage at 2.0 m. The proximity between forests and shrubs were also found to be important in providing
refuge for the birds during winter. Recommendations for conservation management include protecting the existing habitats in
Dongzhai National Nature Reserve, increasing suitable habitat for Reeves’s Pheasant through artificial plantations (e.g. firs),
and restoring some parts of the large shrub area into forests.
__________
Translated from Biodiversity Science, 2005, 13 (5) [译自: 生物多样性, 2005,13(5)] 相似文献
77.
Thymidylate synthase (TS), an essential enzyme for catalyzing the biosynthesis of thymidylate, is a critical therapeutic target in cancer therapy. Recent studies have shown that TS functions as an RNA-binding protein by interacting with two different sequences on its own mRNA, thus, repressing translational efficiency. In this study, peptides binding TS RNA with high affinity were isolated using mRNA display from a large peptide library (>1013 different sequences). The randomized library was subjected up to twelve rounds of in vitro selection and amplification. Comparing the amino acid composition of the selected peptides (12th round, R12) with those from the initial random library (round zero, R0), the basic and aromatic residues in the selected peptides were enriched significantly, suggesting that these peptide regions might be important in the peptide-TS mRNA interaction. Categorizing the amino acids at each random position based on their physicochemical properties and comparing the distributions with those of the initial random pool, an obvious basic charge characteristic was found at positions 1, 12, 17 and 18, suggesting that basic side chains participate in RNA binding. Secondary structure prediction showed that the selected peptides of R12 pool represented a helical propensity compared with R0 pool, and the regions were rich in basic residues. The electrophoretic gel mobility shift and in vitro translation assays showed that the peptides selected using mRNA display could bind TS RNA specifically and inhibit the translation of TS mRNA. Our results suggested that the identified peptides could be used as new TS inhibitors and developed to a novel class of anticancer agents. 相似文献
78.
Ruihan Zhang Xin Li Zhongjie Liang Kongkai Zhu Junyan Lu Xiangqian Kong Sisheng Ouyang Lin Li Yujun George Zheng Cheng Luo 《PloS one》2013,8(8)
Protein arginine methyltransferase 1 (PRMT1), the major arginine asymmetric dimethylation enzyme in mammals, is emerging as a potential drug target for cancer and cardiovascular disease. Understanding the catalytic mechanism of PRMT1 will facilitate inhibitor design. However, detailed mechanisms of the methyl transfer process and substrate deprotonation of PRMT1 remain unclear. In this study, we present a theoretical study on PRMT1 catalyzed arginine dimethylation by employing molecular dynamics (MD) simulation and quantum mechanics/molecular mechanics (QM/MM) calculation. Ternary complex models, composed of PRMT1, peptide substrate, and S-adenosyl-methionine (AdoMet) as cofactor, were constructed and verified by 30-ns MD simulation. The snapshots selected from the MD trajectory were applied for the QM/MM calculation. The typical SN2-favored transition states of the first and second methyl transfers were identified from the potential energy profile. Deprotonation of substrate arginine occurs immediately after methyl transfer, and the carboxylate group of E144 acts as proton acceptor. Furthermore, natural bond orbital analysis and electrostatic potential calculation showed that E144 facilitates the charge redistribution during the reaction and reduces the energy barrier. In this study, we propose the detailed mechanism of PRMT1-catalyzed asymmetric dimethylation, which increases insight on the small-molecule effectors design, and enables further investigations into the physiological function of this family. 相似文献
79.
用过氧化物酶-抗过氧化物酶(PAP)法,对中华大蟾蜍消化道(冬眠期与非冬眠期),脑及其他组织的5-HT分布进行了研究。5-HT免疫染色细胞位于脑干中缝核区和间脑的第Ⅲ脑室腹侧的室管膜细胞区。阳性神经元呈圆形或卵圆形,细胞常有突起与其他阳性细胞突起相连,上述部位中还有一些阳性神经纤维。消化道的免疫染色细胞密度在胃幽门、胃体和胃贲门处最高,食道和十二指肠次之,大肠和小肠最低。非冬眠期蟾蜍消化道内免疫染色细胞密度明显高于冬眠期的(P<0.05)。阳性细胞位于粘膜上皮或腺上皮细胞间,细胞有一个或一个以上呈阳性反应的突起,有的突起伸入肠腔面或腺腔面,有的穿过基膜到达固有层,表明这些细胞兼有内、外分泌的功能。在甲状旁腺的主细胞间,肺呼吸性细支气管上皮和肺泡管上皮细胞间都有5-HT免疫染色细胞,细胞呈立方形、圆形、卵圆形或不规则形,常有几个细胞成簇分布。 相似文献
80.
Alpha7 nicotinic acetylcholine receptor (nAChR), an essential regulator of inflammation, is abundantly expressed in hippocampal neurons, which are vulnerable to bacterial meningitis. However, it is unknown whether α7 nAChR contributes to the regulation of these events. In this report, an aggravating role of α7 nAChR in host defense against meningitic E. coli infection was demonstrated by using α7-deficient (α7(-/-)) mouse brain microvascular endothelial cells (BMEC) and animal model systems. As shown in our in vitro and in vivo studies, E. coli K1 invasion and polymorphonuclear neutrophil (PMN) transmigration across the blood-brain barrier (BBB) were significantly reduced in α7(-/-) BMEC and α7(-/-) mice. Stimulation by nicotine was abolished in the α7(-/-) cells and animals. The same blocking effect was achieved by methyllycaconitine (α7 antagonist). The tight junction molecules occludin and ZO-1 were significantly reduced in the brain cortex of wildtype mice infected with E. coli and treated with nicotine, compared to α7(-/-) cells and animals. Decreased neuronal injury in the hippocampal dentate gyrus was observed in α7(-/-) mice with meningitis. Proinflammatory cytokines (IL-1β, IL-6, TNFα, MCP-1, MIP-1alpha, and RANTES) and adhesion molecules (CD44 and ICAM-1) were significantly reduced in the cerebrospinal fluids of the α7(-/-) mice with E. coli meningitis. Furthermore, α7 nAChR is the major calcium channel for nicotine- and E. coli K1-increased intracellular calcium concentrations of mouse BMEC. Taken together, our data suggest that α7 nAChR plays a detrimental role in the host defense against meningitic infection by modulation of pathogen invasion, PMN recruitment, calcium signaling and neuronal inflammation. 相似文献